Various methods are known for administering pharmaceutically active agents to a host in need of treatment. For example, such agents are often administered topically, parenterally, orally, ocularly, or nasally, depending upon the nature of the illness being treated.
The therapeutic activity of a pharmaceutical agent administered in one of these manners is often influenced both by passive availability, namely the ability of the pharmaceutically active agent to be released from the carrier composition used to administer the agent, and by biological availability, namely the agent's ability to pass through a membrane. The lesser of these typically determines the speed of absorption of a pharmaceutically active agent by an organism.
In the case of topical applications, for example, the pharmaceutically active agent must be released from the carrier composition and partition into and penetrate the epidermis of the skin before it can be absorbed and transferred to elicit its pharmacological effects. Generally, passage through the epidermis is the slowest and consequently the rate-determining step. Enhanced passage through the epidermis is often attempted by selecting carrier compositions tailored to the particular pharmaceutically active agent being administered.
Various methods are known for improving the absorbability of poorly absorbable pharmaceutically active agents. For example, absorbability in some cases is improved through a technological treatment of the pharmaceutically active agent, e.g., by means of micronization or complex-formation, or through the addition of solubility improving additives.
These techniques, however, exhibit many disadvantages. For example, these techniques often require the use of special apparatuses or process steps during preparation, and some of these techniques are successful for only a limited number of pharmaceutically active agents. Furthermore, only a limited number and amount of additives may be employed in certain cases due to safety and/or compatibility problems.
There is therefore a need in the art for formulations which provide a high degree of absorption, when applied topically, parenterally or orally, for pharmaceutically active agents which are themselves per se poorly absorbable or highly insoluble.
Furthermore, there is a need in the art for formulations which are optimally effective in delivering lipophilic, pharmaceutically active agents in a solubilized form to a host for treating skin dermatoses such as psoriasis. Psoriasis is a nonmalignant skin disease of abnormal cell proliferation and is among the dermatoses having a poorly understood etiology. Although many antimetabolites are known to be active against psoriasis, many are mutagenic or carcinogenic analogs. Therefore, there is a particular need in the art for non-carcinogenic, pharmaceutically active compounds which are effective in treating psoriasis.
Pharmaceutically active agents effective in treating dermatological conditions are typically incorporated in a suitable oil or water based ointment, lotion or cream vehicle to promote uniform application and effective transdermal absorption. In the past, oil-based vehicles for topical medicaments have suffered several drawbacks. For example, many oil-based vehicles are not water washable and have a tendency to adhere to and stain clothing. Furthermore, the greasy nature of many oil-based compositions served to inhibit the release and subsequent absorption of many topically pharmaceutically active agents.
To overcome the defects described above, several water-based formulations have been developed which are water washable, non-staining, and which provide satisfactory spreadability and adherence while not inhibiting the release of pharmaceutically active agents incorporated therein. These water-based formulations, however, also suffer drawbacks in that they are not suitable for use with pharmaceutically active agents which are water-decomposable or water-insoluble.